It is often desirable to deliver therapeutic agents into the vascular system of a patient's body to treat medical conditions, such as stenosis and other diseases of the vessel, and to prevent the reoccurrence of these conditions; however, the site-specific delivery of these agents presents many challenges. Known methods for treating stenosis and other diseases of the vessel include the delivery of anti-proliferative agents, anti-inflammatory agents, and thrombolytics by infusing the agents into the blood vessels using an infusion catheter. In addition, infusion catheters have been equipped with a porous perfusion balloon, electrode and/or heating elements on or in the balloon to cause electroporation or to heat the surrounding tissue to improve drug delivery. However, infusion catheters equipped as described have many potential problems, including too large a dose is required (which causes systemic toxicity), too long an exposure time is required, and direct vessel injury can occur from electrodes, heating elements, etc.
In an effort to avoid some of the problems with infusion delivery, the therapeutic agent can be delivered to the vascular site by leaching or extravascular methods. The therapeutic agent can be embedded in or deposited on a catheter, on the wall of a non-porous balloon or in a coating on the catheter or a stent. These methods can prevent the formation of plaques and/or narrowing of the vessel. However, the coating can chip off during delivery and migrate to undesired locations. In addition, a major drawback of a coating is that continued leaching prevents proper vessel healing, leading to thrombosis. Extravascular methods such as injecting therapeutic agents directly into a desired tissue region or attaching a polymer gel or drug-soaked sponge to the outside of a vessel are known. The injection of therapeutic agents would likely result in the contact of the therapeutic agent with healthy tissue and lead to diffusion problems similarly associated with the infusion catheter. In addition, these extravascular methods are very invasive and can not be applied to inaccessible vessels.
In each case, the dilution or “washing-out” of the therapeutic agent is a major disadvantage. This “washing-out” can potentially result in the removal of therapeutic agent from the desired treatment site before an effective amount has been absorbed by the diseased vessel. This not only reduces the effectiveness of the treatment by preventing the therapy from reaching the target site, but it also results in the constant discharge of therapeutic agent into the blood stream where it can potentially cause serious side effects. To offset the dilution, an increased volume or concentration is often used which further intensifies concerns for possible side effects.
Another concern associated with known methods for the local delivery of very potent therapeutic agents, such as paclitaxel, is that too much drug is absorbed into the vessel wall due to a high local concentration or too little drug is absorbed into the vessel wall due to a low local concentration. Many drugs have a narrow concentration window at which the drug is effective. A slightly higher concentration can have toxicity effects and a slightly lower concentration can render the treatment ineffective. In order to provide an efficacious concentration to the treated site, a homogeneous delivery of the drug to the treatment site is desired. Without this homogeneous delivery, the administration of such medication often produces adverse side effects or results in some vessel regions where the disease is not sufficiently treated or prevented.
Thus, a need exists for improved methods for the site-specific delivery of therapeutic agents to the vascular system.